7. Project Summary: The prevalence of cannabis use disorder (CUD) in people with schizophrenia is estimated to be 25-50%, and CUD in these patients is associated with poorer functional outcomes, early onset of psychosis and symptoms exacerbation, and higher rates of psychiatric hospitalization. There are few, if any, validated treatments for CUD in this population. Patients with schizophrenia also have wide-ranging deficits in neurocognitive function, which may be altered by cannabis use in a negative manner. However, brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) may hold promise for reducing cannabis use and improving neurocognition (e.g., working memory, attention) in patients with schizophrenia. Preliminary experience from our laboratory and elsewhere have shown that schizophrenia patients with co-morbid CUD tolerate rTMS procedures with minimal adverse events, that they can be retained in short-term intervention trials, and that working memory deficits, drug use, withdrawal and craving may be reduced by high-frequency (20 Hz) rTMS procedures. The proposed R21 study would test the effects of active (n=20) versus sham (n=20) high frequency rTMS (20 Hz) delivered by a standard Figure-8 TMS coil on cannabis use and cognitive outcomes in a total of N=48 patients with schizophrenia and co-morbid CUD, in a 6-week, double-blind, randomized, parallel groups controlled trial. All subjects would receive contingency management and drug counseling interventions to encourage trial endpoint cannabis abstinence, which we have shown to be effective in the schizophrenia CUD population. The primary outcome measure would be trial endpoint self-reported cannabis use assessed by timeline follow-back confirmed by cannabis urine toxicology. Secondary outcome measures include neurocognitive outcomes (e.g., verbal memory and learning, working memory), cannabis craving and withdrawal and psychosis symptom ratings (Positive and Negative Symptoms Scale, Calgary Depression Scale for Schizophrenia). We predict that active versus sham rTMS would significantly reduce cannabis use and increase trial endpoint negative cannabis urine frequency, and improve neurocognitive outcomes such as verbal learning and memory and working memory, as well as reductions in withdrawal and craving, positive and negative symptoms of psychosis in schizophrenia. The significance of this study is that a novel neuroscience-based treatment for co-morbid CUD and schizophrenia may be developed for use in the clinic, and reduce the burden of this important co-morbidity which is associated with serious functional impairment in schizophrenia.